PATHOGENETIC MECHANISMS IN FELINE LEUKEMIA

该计划的长期目标是确定多个事件， 在国内淋巴系统恶性肿瘤发病机制中的相互作用 这种远交种有白血病淋巴瘤的发病率最高 任何动物，和水平感染的自然发生的猫科动物 白血病病毒（FeLV）是导致其对 白血病发生对于发生的事件还有很多有待发现的地方 在长期的病毒血症期间。目前的证据表明 感染性FeLV和非感染性FeLV之间的重组事件 内源性遗传的FeLV样元件，其产生高致病性 变异病毒很可能重组病毒表面 糖蛋白，其提供对预期靶细胞的识别， 病毒也可以以相同或变异形式对 细胞增殖/胚细胞发生和细胞病变。的其他因素 包括插入激活的 细胞基因如c-myc和flvi-2，以及增加的 通过病毒突变增强转录活性 转录调控元件FeLV的免疫活性受损- 受感染的猫也会导致肿瘤的发展。 建议继续开展关于分子理解的研究， 决定靶细胞嗜性、疾病 特异性和免疫抑制特性。单个重组 病毒将从致病性病毒混合物和从 选择自然发生的淋巴肉瘤， 遗传结构，以及体外和体内生物学和病理学 特性.实验的目的是检验 嵌合病毒糖蛋白通过直接或 间接影响细胞增殖、分化或凋亡。 此外，适当的猫淋巴肉瘤标本代表 大多数未鉴定的前病毒插入位点已经被鉴定， 选择，分析应该提供线索FeLV中的新基因- 诱发肿瘤性疾病。 这些相互关联的研究结合起来，应该会带来新的见解。 逆转录病毒诱导的淋巴癌的发病机制， 动物种类。

The long-term goal of this program is to identify the multiple events that interplay in the pathogenesis of lymphoid malignancies in the domestic cat. This outbred species has the highest incidence of leukemia-lymphoma of any animal, and horizontal infection of the naturally occurring feline leukemia virus (FeLV) is responsible for its increased susceptibility to leukemogenesis. Much remains to be discovered for the events that occur during the prolonged viremic period. Current evidence suggests recombinational events between the infectious FeLV and non-infectious endogenously inherited FeLV-like elements which generate highly pathogenic variant viruses. It is likely that the recombinant viral surface glycoproteins which provide recognition of the prospective target cell by the virus may also have independent effect in the same or variant forms on cell proliferation/blastogenesis and cytopathicity. Other factors that contribute to neoplastic disease include the insertionally activated cellular genes such as c-myc and flvi-2 and the gaining of increased strength in transcriptional activity through mutations in viral transcription regulatory elements. Impaired immunologic activity in FeLV- infected cats also has consequences in tumor development. It is proposed to continue the studies on the molecular understanding of the recombinational parameters that dictate target cell tropism, disease specificity, and immunosuppressive properties. Individual recombinant viruses will be molecularly cloned from pathogenic virus mixtures and from selected naturally occurring lymphosarcomas for the scrutiny of their genetic structure, and in vitro and in vivo biological and pathological properties. Experiments have been designed to examine the potential that chimeric viral glycoproteins contribute to pathogenesis by directly or indirectly influencing cell proliferation, differentiation or apoptosis. In addition, appropriate feline lymphosarcoma specimens representing mostly uncharacterized provirus insertion sites have been identified and selected, analysis of which should provide clues to novel genes in FeLV- induced neoplastic disease. These interconnected studies, in combination, should lead to new insights into the pathogenesis of retrovirus-induced lymphoid cancer in an outbred animal species.